A variety of chemical agents having therapeutically interesting activity have been isolated from natural sources. Many of these are availabel in only minute quantities. This proposal details new synthetic methods that will lead to the total synthesis of three of these, the pseudoguanolide sesquiterpene amarilin, the diterpene forskolin, and the cardiotonic and myotonic alkaloid pumiliotoxin-B. These methods will be general application in the synthesis of complex natural products.